Large Testosterone Blood Level Variations Found with the Use of Androgel

[Nelson Vergel]

Serum Testosterone (T) Level Variability in T Gel- Treated Older Hypogonadal Men: Treatment Monitoring Implications


Ronald S. Swerdloff et al

doi: 10.1210/JC.2015-1542 J Clin Endocrinol Metab



Context: The optimal frequency for on-treatment serum testosterone (T) measurement used for dose adjustment after transdermal T gel application is unknown, especially in older men with thinner skin and slower metabolic clearance.

Objectives: To determine variability of post-gel application serum T concentrations and assess whether single levels are reflective of average serum T concentrations over 24h (Cavg0 –24).
Design: A double-blinded, placebo-controlled randomized trial.

Setting: 5 academic centers.

Participants: 47 symptomatic men 65 y.o. with average of two morning T concentration <275 ng/dl.

Intervention(s): Transdermal T or placebo gel was applied for 120 + or - 14 days. Monthly dose adjustments were made if necessary to target serum T between 400/500 to 800 ng/dl.

Main Outcome Measures: Variability of serum T 2h post-gel application on 2 outpatient visits and at multiple time-points over 24h during the inpatient day.

Results: On-treatment T levels varied substantially on the two ambulatory days and over 24h during the inpatient day. Ambulatory 2h post-application T levels did not correlate significantly with either 2h post-application serum T or Cavg0 &#8211;24 measured during the inpatient day. Only 22.2% of men receiving T had Cavg0 &#8211;24 within the target range of 500 &#8211; 800ng/dl; 81.5% had Cavg0 &#8211;24 within the broader 300 &#8211;1000ng/dl range.

Conclusion: Large within-individual variations in serum T after T gel application render ambulatory 2h post-application T level a poor indicator of average serum T on another day. Our data point out the limitations of dose adjustments based on a single post-application serum T measurement.

 

[HarryCat]

So basically that is implying that if you are on gel then serum testing is useless and you're probably better off dosing based on symptoms.

Or am i missing something?

 

[Nelson Vergel]

It means that there can be a drastic difference in blood levels of T in the same man on the same day and 2 hours after application of the gel. The variation does not decrease with time. The authors could not explain why.

Some men (the ones of the left hand side cluster) had smaller variations than the right hand side cluster.

This variation can make it difficult for titrating dose since blood levels are not as constant as the Androgel label explains.

They did not measure subcutaneous fat content.

 

[Nelson Vergel]

Here is an interesting review of prescription data that is not very encouraging about Androgel or Testim testosterone gels.

Most Men on Androgel and Testim Stop Using Them

 

[Brooksy Chuck]

anything on Axiron? my endo suspects the enthanol in axiron enables better absorption?

 

[Nelson Vergel]

Muram D, Ni X.

Utility of a Single Serum Testosterone Measurement to Determine Response to Topical Testosterone Replacement in Hypogonadal Men.

Curr Med Res Opin. http://www.tandfonline.com/doi/abs/10.1185/03007995.2015.1117434


OBJECTIVE: To evaluate the utility of single serum testosterone measurements in patients receiving transdermal testosterone therapy.


RESEARCH DESIGN AND METHODS: Data were from an open-label, 120-day, multi-center titration trial in androgen-deficient men receiving an initial daily dose of 60 mg testosterone (testosterone topical solution 2%) applied to axillae (30 mg/axilla). Average concentration (Cavg) of serum testosterone (TT) was determined on days 15, 60, and 120; doses were adjusted to maintain normal Cavg (300-1050 ng/dL [10.4-36.4 nmol/L]). Accuracy of single serum TT measurements (2, 4, 8, 12, 16, and 20 hours post-dose) was assessed in patients with Cavg TT within and below (<300 ng/dL [<10.4 nmol/L]) the normal range.


CLINICAL TRIAL REGISTRATION: Clinicaltrials.gov - NCT00702650


MAIN OUTCOME MEASURE: Serum testosterone levels.


RESULTS: In patients with normal Cavg (n=85), 79% to 92% had serum testosterone levels within normal range 2, 4, 8, 12, 16, and 20 hours post-dose; significant effects of time post-dose single testosterone measurement accuracy (P=0.01) were observed: testing accuracy peaked 4 to 8 hours post-dose and tapered approximately 16 hours post-dose. In 28/63 instances with low Cavg TT throughout the study a normal 2-hour serum TT level was observed.


The average percentage (across all days) of discordant results between Cavg (<300 ng/dL [<10.4 nmol/L]) and single serum TT measurements (300-1050 ng/dL [10.4-36.4 nmol/L]) declined with increasing time from dose application (44% at 2 hours, 38% at 4 hours, 22% at 8 hours, 3% at 16 hours).


CONCLUSIONS: Reliance on a single serum testosterone measurement to determine the need for dose adjustment of testosterone topical solution 2% may lead clinicians to change the dose unnecessarily, or alternatively, not increase the dose when necessary. The results reported here are limited to testosterone topical solution 2% and may not be applicable to other topical agents.

 

[Encore]

Another related point is regarding the desirability of wide variation in T levels. Dr. Crisler has often stated that young men have wide variation in T levels throughout the day and gels produce such wide variation. If the goal is to produce a hormonal environment similar to that of a young, healthy man, gels are the preferable solution.

 

[Henry]

Hi,
I'm just wondering, is it a bad thing to be level? Let's say, for instance, I'm taking my dose every 3.5 days, etc. That will keep me at a steady level with little variation. I know Dr. Crisler says that variation is great because it mimics the hormones of a young, healthy male but is the steady level that bad?

 

[Vince]

Hi,
I'm just wondering, is it a bad thing to be level? Let's say, for instance, I'm taking my dose every 3.5 days, etc. That will keep me at a steady level with little variation. I know Dr. Crisler says that variation is great because it mimics the hormones of a young, healthy male but is the steady level that bad?

Personally for me I love a steady level of testosterone, no spikes. But that's my opinion and I do know Dr. Crisler is an excellent doctor.

 

[Encore]

Hi,
I'm just wondering, is it a bad thing to be level? Let's say, for instance, I'm taking my dose every 3.5 days, etc. That will keep me at a steady level with little variation. I know Dr. Crisler says that variation is great because it mimics the hormones of a young, healthy male but is the steady level that bad?

Henry,

I don't think we will ever know whether it is "good" or "bad" to have variation. I think Dr. Crisler's attempt to mimic young, healthy men's variability makes sense intuitively and that will probably be debated for the next 50 years as we learn more.

Some men say that they feel better with less variation, but there may be tradeoffs that are currently unknown.